Oral Glutamatergic Augmentation for Trauma-Related Disorders with Fluoxetine- / Bupropion- Potentiated Dextromethorphan ± Piracetam: A Four-Patient Case Series

A brief oral regimen combining dextromethorphan with fluoxetine, sometimes plus piracetam or bupropion, produced rapid and lasting remission in four patients with hard-to-treat trauma-related disorders, including somatic PTSD, bereavement-related PTSD, adolescent depression, and complex PTSD with bipolar II and borderline features. Within days to weeks, intrusive memories, rumination, somatic pain, and disability sharply declined, with no dissociation, hypertension, or mania. The findings extend the ketamine/Auvelity treatment framework to trauma-spectrum illnesses and support controlled trials of low-cost NMDA–AMPA modulators for PTSD prevention and treatment.

Study at a glance

Abstract

Abstract Traditional monoaminergic medications often offer limited relief for the physical and cognitive symptoms of post-traumatic stress disorder (PTSD) and complex PTSD. Growing data now point to fast-acting, glutamate-based treatments that boost synaptic plasticity and interrupt fear-conditioned neural circuits. We report four sequential cases of hard-to-treat trauma-spectrum disorders—somatic PTSD, acute bereavement-related PTSD, trauma-linked adolescent depression, and complex PTSD complicated by bipolar II disorder, ADHD, and borderline features—that achieved swift, long-lasting remission with an inexpensive, fully oral protocol centered on dextromethorphan (DXM) potentiated by fluoxetine, with optional add-on piracetam and/or bupropion. Within days to weeks, all four patients showed striking declines in intrusive memories, rumination, somatic pain, and functional disability, and none experienced dissociation, hypertension, or mania. These findings broaden the ketamine/Auvelity framework to trauma-related illnesses and highlight the need for controlled studies of low-cost, readily available NMDA–AMPA modulators for both the prevention and treatment of PTSD.